Terson''s syndrome in a patient with acute promyelocytic leukemia on all-trans retinoic acid treatment

Hypothermia induced by surface cooling has shown to protect vulnerable regions of the brain during an ischemic insult. This study evaluated the neuroprotective efficacy of neurotensin, a potent hypothermic agent, using a 5-min carotid occlusion procedure in the gerbil. In Experiment 1, the dose-response and time course of neurotensin-induced hypothermia were evaluated (n = 5/dose). Central infusion of 10, 20, and 30 micrograms neurotensin were found to significantly decrease core body temperature of conscious gerbils within 30 min of administration. In Experiment 2, gerbils pretreated with 30 micrograms neurotensin were permitted to become hypothermic or were maintained at 37 degrees-38 degrees C (rectal) during ischemic insult. Other gerbils were pretreated with peptide vehicle prior to ischemic insult (at 37 degrees -38 degrees C) or underwent a sham procedure (n = 6/condition). At 24 h after surgery, gerbils were tested for increased locomotor activity in an open-field apparatus. Gerbils pretreated with peptide vehicle or neurotensin and maintained at 37 degrees-38 degrees C during ischemia had significantly higher activity levels compared to the other treated groups. In contrast, gerbils made hypothermic with neurotensin exhibited activity levels similar to sham gerbils. Histological assessment revealed that neurotensin-induced hypothermia protected the CA1 region from ischemic damage.     

Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management

Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines

Spontaneous proliferative liver lesions were found in 15 (13 males and 2 females) of 244 (122 of each sex) transgenic (Tg) mice carrying the human prototype c-H-ras gene (rasH2). The liver lesions included 3 foci of cellular alteration, 1 hepatocellular adenoma, 5 hepatocellular carcinomas, and 4 hepatic hemangiosarcomas in the males and 1 focus of cellular alteration and 1 hepatocellular carcinoma in the females. The mutation patterns of the human and endogenous mouse c-H-ras codon 61 in these proliferative liver lesions were analyzed by DNA amplification using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP), and oligonucleotide dot blot hybridization. The hepatocellular carcinomas in 4 males and 1 female contained a point mutation in the mouse c-H-ras gene: 3, 1, and 1 carcinomas had a CAA to AAA transversion at the first base of codon 61, a CAA to CTA transversions, and a CAA to CGA transition at the second base of codon 61, respectively. No point mutations in the human c-H-ras transgene were detected in any hepatocellular carcinoma. All 4 hepatic hemangiosarcomas had a CAG to CTG transversion at codon 61 of the human c-H-ras gene, but no point mutations were detected in codon 61 of the mouse c-H-ras gene. No mutations in human or mouse c-H-ras codon 61 were detected in altered cell foci or hepatocellular adenoma. These results indicate that spontaneous liver tumors in rasH2 Tg mice contain different mutation patterns depending on the histologic type or cell origin of the tumors (i.e., hepatocellular carcinomas or hepatic hemangiosacomas). The absence of similar mutations in foci of cellular alteration and the hepatocellular adenoma suggests that the occurrence of codon 61 point mutations is a late event in the progression of hepatocellular neoplasia in rasH2 Tg mice.     

Bryostatin 1 induces ubiquitin COOH-terminal hydrolase in acute lymphoblastic leukemia cells

It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pl 34-5.3) was detected by 2 D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2 D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated cells and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.     

The contrast enhancement of brain and spinal cord tumors using Gd-DTPA in magnetic resonance tomography with an extra-low magnetic-field intensity

The contrasting agent Gd-DTPA (Magnevist, Schering AG, Germany) was tested when used in magnetic resonance tomography using extra-low (0.04 T) magnetic field intensity in 68 patients with various brain and spine tumors. The agent was injected intravenously in a dose of 0.1 mmol/kg. No complications were found. The tests showed its high efficiency in the diagnosis of brain neoplasms (particularly in malignant intracerebral disorders, meningiomas and neurinomas). Benign astrocytomas induced no noticeable signal intensification on post-contrasting T1-weighed tomograms. In all cases of spinal tumors, the application of Gd-DTPA could specify the extent of tumor invasions, the presence of cysts and identify accessory tumor nodes in one case.     

Recent developments in the synthesis and discovery of oligosaccharides and glycoconjugates for the treatment of disease

The development of the first automated oligosaccharide synthesizer, along with new methods for screening carbohydrate ligand arrays is likely to lead to a rapid acceleration in both our ability to synthesize these molecules, and understand the roles of oligosaccharides and glycoconjugates in biology. Consequently we may uncover new avenues for therapeutic intervention more rapidly. These recent developments are very important since our understanding of the role of glycoconjugates in nature has traditionally fallen far behind that of the other biopolymers such as proteins and nucleic acids as the formation of, for example, glycosylated proteins is not template driven. The chemical synthesis of oligosaccharides and glycoconjugates has provided us with new potential cancer vaccines, antibiotics and new biotechnological tools. Glycobiologists have employed many such tools to uncover new signalling roles for oligosaccharides and glycoconjugates. In this review we aim to highlight some emerging methods for glycoconjugate assembly and screening, and discuss innovative approaches to glycoconjugate based drug design and delivery, all of which are, and will continue to be, fruitful avenues for medicinal chemistry research.     

Poly-(L-lactic) acid membranes in palatal surgery in beagle dogs: clinical and histologic evaluation

This article reports on the histologic findings from a larger study that was designed to investigate whether the attachment of scar tissue to underlying bone, which is normally found after palatal surgery, can be prevented by using biodegradable poly-(L-lactic) acid membranes. Von Langenbeck's procedure was simulated in 12-week-old beagle dogs without clefts. In one group normal wound healing was allowed. In two groups, membranes were inserted immediately after surgery or 3 weeks thereafter. Sham and control groups were also included. Histologic evaluation was carried out at regular intervals. Reports have been published on other aspects, such as clinical wound healing, contraction and maxillary arch development in beagle dogs following this treatment. After direct implantation of membranes, wound healing was retarded. Disintegration of the membranes started soon after implantation and remaining particles were surrounded by a fibroblastic sheath and a fibrous capsule. At sites where membrane particles persisted, attachment of the scar tissue to the underlying bone by Sharpey's fibers was prevented.